Evidence map›Paper›PMID 29885030›Full record

ArticleMolecular microbiology2018

Identifying a novel connection between the fungal plasma membrane and pH-sensing.

Hannah E Brown, Kyla S Ost, Shannon K Esher, Kaila M Pianalto, Joseph W Saelens, Ziqiang Guan, J Andrew Alspaugh

Abstract read
In one paragraph

Article in Molecular microbiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed.

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  15. Review
  16. Role of lipid transporters in fungal physiology and pathogenicity.Computational and structural biotechnology journal · 2019
    Review
  17. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Hannah E BrownDepartments of Molecular Genetics and Microbiology/Medicine, Duke University School of Medicine, Durham, NC, USA.
Kyla S OstDepartments of Molecular Genetics and Microbiology/Medicine, Duke University School of Medicine, Durham, NC, USA.
Shannon K EsherDepartments of Molecular Genetics and Microbiology/Medicine, Duke University School of Medicine, Durham, NC, USA.
Kaila M PianaltoDepartments of Molecular Genetics and Microbiology/Medicine, Duke University School of Medicine, Durham, NC, USA.
Joseph W SaelensDepartments of Molecular Genetics and Microbiology/Medicine, Duke University School of Medicine, Durham, NC, USA.
Ziqiang GuanDepartment of Biochemistry, Duke University School of Medicine, Durham, NC, USA.
J Andrew AlspaughDepartments of Molecular Genetics and Microbiology/Medicine, Duke University School of Medicine, Durham, NC, USA.

Funding

ORGANIZATION AND FUNCTIONS OF CELLULAR STRUCTUREST32GM007184 · NIGMS · DUKE UNIVERSITY · PI JINKS-ROBERTSON, SUE · 1985 to 2019
$18.2M
Rapid production of SARS-CoV-2 molecular clones using CRISPR-based yeast recombineeringR01AI100272 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MADHANI, HITEN D · 2012 to 2025
$11.3M
Trehalose Pathway for Antifungal Targets and InhibitorsP01AI104533 · NIAID · DUKE UNIVERSITY · PI BRENNAN, RICHARD GERALD · 2015 to 2019
$9.0M
Coordinated Regulation of Virulence Genes in C. neoformansR01AI074677 · NIAID · DUKE UNIVERSITY · PI ALSPAUGH, ANDREW, WORMLEY, FLOYD L. · 2011 to 2020
$4.0M
Defining pH-Sensing in Fungal VirulenceF31AI140427 · NIAID · DUKE UNIVERSITY · PI BROWN, HANNAH ELIZABETH · 2019 to 2020
$77k
NIAID NIH HHS F31 AI140427NIAID NIH HHS P01 AI104533NIAID NIH HHS R01 AI074677NIAID NIH HHS R01 AI100272NIGMS NIH HHS T32 GM007184
6 · The paper itself

Abstract

The mechanisms by which micro-organisms sense and internalize extracellular pH signals are not completely understood. One example of a known external pH-sensing process is the fungal-specific Rim/Pal signal transduction pathway. Fungi, such as the opportunistic pathogen Cryptococcus neoformans, use Rim signaling to sense and respond to changes in environmental pH. Mutations in this pathway result in strains that are attenuated for survival at alkaline pH, and often for survival within the host. Here, we used an insertional mutagenesis screen to identify novel genes required for C. neoformans growth at host pH. We discovered altered alkaline pH growth in several strains with specific defects in plasma membrane composition and maintenance of phospholipid assembly. Among these, loss of function of the Cdc50 lipid flippase regulatory subunit affected the temporal dynamics of Rim pathway activation. We defined distinct and overlapping cellular processes regulated by Rim101 and Cdc50 through analysis of the transcriptome in these mutant strains. We further explored how pH-induced membrane changes affect membrane-bound pH-sensing proteins, specifically the C-terminal domain of the Rra1 protein, an upstream Rim pathway activator and pH sensor. These results suggest both broadly applicable and phylum-specific molecular interactions that drive microbial environmental sensing.

Indexed as

Hydrogen-Ion ConcentrationAcetyltransferasesCell MembraneCryptococcus neoformansDNA-Binding ProteinsFungal ProteinsGene Expression ProfilingMutagenesis, InsertionalP-type ATPasesSignal TransductionAcetyltransferasesCdc50 protein, Cryptococcus neoformansDNA-Binding ProteinsFungal ProteinsP-type ATPases

Identifiers

PMID29885030
PMCPMC6173979

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.